Effects of Endocrine Disrupting Chemicals on Thyroid Hormone Binding

已经确定的是，一些外源性内分泌干扰化学品、多氯联苯、二苯并对二恶英及其羟基化合物等多卤代芳烃可影响哺乳动物的甲状腺系统。然而，这些化学品与甲状腺素运载蛋白结合的影响在大型真兽目动物中低于其他脊椎动物，因为甲状腺素运载蛋白对上述化学品具有很高的亲和力，是啮齿动物、鸟类、两栖动物和鱼类血浆中主要甲状腺素结合活性的原因。在本研究中，我们已经调查了几类化学品与两栖动物和鸟类甲状腺素运载蛋白和甲状腺受体的相互作用。将纯化的甲状腺素运载蛋白与[^<125>I]-3，3，5 '-三碘甲状腺原氨酸（T_3）在工业、医学或农业化学品的存在下孵育。为了阐明化学品与甲状腺素运载蛋白的相互作用模式，表观解离常数a ...更多信息 通过Scatchard图确定最大结合容量。[^<125>I]T_3摄取到红细胞中也进行了研究，在不同浓度的一些化学品的存在下。合成雌激素己烯雌酚取代甲状腺素运载蛋白中的[^ I]T_3的能力是T_3的2-50倍<125>。农用化学品碘苯腈和五氯苯酚也是[^<125>I]T3与甲状腺素运载蛋白结合的显著抑制剂。Scatchtd分析表明，这些化学品的结合模式是竞争性的。有趣的是，一种杀螨剂三氯杀螨醇在浓度为10 μ M至10 μ M时，可激活[^<125>I]T_3与牛蛙甲状腺素运载蛋白的结合，激活程度高达2倍<-9><-6>。与<125>牛蛙甲状腺素运载蛋白相比，鸡甲状腺素运载蛋白与T_3的结合受到大多数化学物质的深刻影响，牛蛙甲状腺素运载蛋白是强T_3载体。然而，甲状腺受体对这些化学物质的亲和力很弱或很小。总之，甲状腺素运载蛋白识别几种内分泌干扰化学品的物种特异性的方式。某些雌激素与甲状腺素运载蛋白的结合不仅可以调节它们进入细胞的途径，而且可以改变细胞外游离T_3 Less的浓度

It is well established that some exogenous endocrine disrupting chemicals, polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls, dibenzo-p-dioxins and their hydroxylated compounds, can affect a mammalian thyroid system. However, the impact of the chemicals' binding to transthyretin is lower in large eutherians than in other vertebrates, because a thyroid-hormone-binding protein, tranthyretin, which has an high affinity for the above chemicals, is responsible for major thyroid hormone-binding activity in plasma of rodents, birds, amphibians and fish. In the present study, we have investigated the interactions of several classes of chemicals with amphibian and avian transthyretins and thyroid receptors. Purified transthyretins were incubated with [^<125>I]-3,3,5'-triiodothyronine (T_3) in the presence of either an industrial, a medical or an agricultural chemical. To clarify the mode of interaction of the chemicals with transthyretins, apparent dissociation constants a … More nd maximum binding capacities were determined by Scatchard plots. [^<125>I]T_3 uptake into red blood cells was also investigated in the presence of various concentrations of some chemicals. A synthetic estrogen, diethylstilbestrol, was 2-50 times more potent than T_3 to displace [^<125>I]T_3 from transthyretin. Agricultural chemicals, ioxynil and pentachlorophenol, were also significant inhibitors on [^<125>I]T3 binding to transthyretins. Scatchatd analyzes indicated that the binding mode of these chemicals was competitive. Interestingly, a miticide dicofol activated [^<125>I]T_3 binding to bullfrog transthyretin up to 2-fold at 10^<-9> to 10^<-6> M. [^<125>I]T_3 binding to chicken transthyretin was profoundly affected by most chemicals investigated here, compared with bullfrog transthyretin which is strong T_3 carrier. However, thyroid receptors showed very weakly or little affinity forthese chemicals. In conclusion, transthyretins recognized several endocrine disrupting chemicals in a species-specific manner. The binding of some estrogenic chemicals to transthyretin may modulate not only their access to the cells but also change the free concentration of extracellular T_3 Less